Metronomic Chemotherapy in Elderly Non-fit Patients With Aggressive B-Cell Lymphomas

Inclusion Criteria:

* Histologically confirmed diagnosis of aggressive Non-Hodgkin Lymphomas (NHLs) including:

  * LBCL1
  * DLBCL;
  * Grade IIIb follicular lymphoma;
  * BL1;
  * B-Cell unclassifiable lymphomas with features intermediate between DLBCL and BL or between DLBCL and Hodgkin's lymphoma (HL)35;
  * High grade B-cell lymphomas1
* Age \>65 years
* Unfit or frail patients (the latest defined, for the purpose of this study, as those who have a maximum of 1 frail factor) according to the multidimensional geriatric evaluation model of the elderly platform of the FIL, who relapsed/progressed after one or maximum two previous lines of treatment or
* "Super-frail" elderly patients at disease onset: eligible super-frail patients are defined, for the purpose of this study, as those who have a maximum of 2 frail factors, according to the CGA adopted in the elderly platform of the FIL, among those below listed:

  * ADL ≤ 4;
  * IADL ≤ 5;
  * Age ≥ 80 years;
  * 1 CIRS grade 3 or \>8 CIRS grade 2.
* Ann Arbor stage I bulky to IV
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* Life expectancy \>1-2 months.
* Adequate renal function (creatinine ≤ 2 mg/dl, unless secondary to lymphoma).
* Adequate liver function (bilirubin ≤ 2 mg/dl, unless secondary to lymphoma).
* Absolute neutrophil count (ANC) ≥1500 cells/mmc and platelets ≥ 50,000 cells/mmc, haemoglobin ≥ 9 gr/dl, unless cytopenia is related to bone marrow involvement by lymphoma.
* Availability of adequate care by family members or other caregivers.
* Written informed consent signature.
* Male Subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 3 months following the end or the discontinuation from the study treatment even if he has undergone a successful vasectomy.

Exclusion Criteria:

* Patients who received more than two previous chemotherapy lines.
* Relapsed/refractory patients with fit profile.
* Fit, unfit, and frail patients at disease onset.
* Malabsorption syndrome or other diseases that affect the ability to swallow oral therapy.
* Concomitant malignancy requiring treatment (except non-melanoma skin cancers and in situ carcinoma of the uterine cervix).
* Presence of opportunistic infections in place.
* Seropositive for or active viral infection with hepatitis B virus (HBV):

  1. HBsAg positive;
  2. HBsAg negative, HBcAb positive with detectable viral DNA (Subjects who are HBsAg negative, HBcAb positive, but viral DNA negative are eligible.
* Seropositive and active infection for hepatitis C virus (subjects who are HCV-RNA negative are eligible).
* Known seropositive for or active viral infection with human immunodeficiency virus (HIV).
* Impossibility to give written informed consent.